1. Field of Invention
This invention relates to drugs for the treatment of mental health problems. More particularly, this invention relates to the use of a drug for the treatment of children who exhibit signs and symptoms of Attention Deficit Syndrome or Attention Deficit Disorder.
2. Prior Art
In this psychopharmacological era characterized by the search for new and more effective agents especially for the treatment of mental health disorders, it has become increasingly important to individually tailor the drug treatment program to achieve the maximum benefit for each patient.
Recently particular attention has been directed to the treatment of the mental health problems of children. One particular mental health condition in children that is receiving extensive investigation is Attention Deficit Syndrome (ADS) also known as Attention Deficit Disorder (ADD) in children. These conditions may or may not be associated with hyperactivity.
The problem is characterized by:
a. Inattention. At least three of the following: PA1 b. Impulsivity: At least three of the following: PA1 c. Hyperactivity. At least two of the following: PA1 d. Onset before the age of 7. PA1 e. Duration of at least six months PA1 f. Not due to schizophrenia, affective disorder, or severe or profound mental retardation.
1. often fails to finish things he or she starts; PA0 2. often doesn't seem to listen; PA0 3. is easily distracted; PA0 4. has difficulty concentrating on schoolwork or other tasks requiring sustained attention; and PA0 5. has difficulty sticking to a play activity. PA0 1. often acts before thinking; PA0 2. shifts excessively from one activity to another; PA0 3. has difficulty organizing work (this not being due to cognitive impairment); PA0 4. needs a lot of supervision; PA0 5. frequently calls out in class; and PA0 6. has difficulty awaiting turn in games or group situations. PA0 1. runs about or climbs on things excessively; PA0 2. has difficulty sitting still or fidgets excessively; PA0 3. has difficulty staying seated; PA0 4. moves about excessively during sleep; and PA0 5. is always "on the go" or acts as if driven by a motor.
Attention deficit disorder without hyperactivity:
The criteria for this disorder are the same as those for attention deficit disorder with hyperactivity except that the individual never has signs of hyperactivity. Diagnostic and Statistical Manual of Mental Health Disorders, Ed. 3, pp. 43-44 (1980); American Psychiatric Association.
Currently, the drugs of choice for ADD or ADS are methylphenidate, whose tradename by CIBA is Ritalin and pemoline whose tradename by Abbott is Cylert. Although Ritalin and Cylert have shown promise in the treatment of ADS and ADD in children, there are certain routine deficiencies in their use such as the highly addictive nature of both drugs, the short active life of both drugs, incomplete control of the symptoms, the "rebound" effect as the drugs wear off late in the day producing increased symptomatology, poor improvement in psycho-social and family involvement, and no improvement in sleep patterns. Further, even when Ritalin and Cylert are effective, alternative drugs should be available to allow the treating physician the option of choosing one drug over others depending on the needs of the individual patient.
During the early to mid 1960's much research was conducted in psychopharmacology in a class of chemicals which were useful in the treatment of depressive symptoms in adults. These compounds were tricylic compounds, more specifically referred to as dibenzocycloheptene derivative compounds. One of this class of antidepressant drugs is N-methyl-5H-dibenzo[a,d]cycloheptene-5-propylamine hydrochloride, medically known as "protriptyline" whose chemical formula is as follows: ##STR1## This product is produced commercially by Merck, Sharp and Dohme under the tradename Vivactil. In the Physicians Desk Reference, published by Edward R. Barnhart on pages 1349 through 1350, (1987), the use of Vivactil tablets is discussed. As stated in that reference, it is an antidepressant agent which is sometimes more effective than other tricylic antidepressant drugs such as imipramine or amitriptyline. It is considered particularly suitable for withdrawn and anergic patients. The drug has some minimal side effects of an anticholinergic nature particularly hypotensive and cardiovascular. However, the reference specifically states that "[t]he drug is not recommended for use with children because its safety and effectiveness in the pediatric age group has not been established."
N-methyl-5H-dibenzo[a,d]cycloheptene-5-propylamine hydrochloride was first disclosed in U.S. Pat. No. 3,244,748, Tishler et. al. where it was described as a drug for the treatment of mental health conditions "as it is an antidepressant and serves as a mood elevator or a psychic energizer." Column 3, lines 38 through 43.
Processes for the production of this product were disclosed in U.S. Pat. No. 3,271,451, Tishler et. al and U.S. Pat. No. 3,513,201, Tishler et. al. Other related chemical compounds also used in the treatment of mental health conditions are disclosed in Kollonitsch, U.S. Pat. No. 3,324,170; Engelhardt, U.S. Pat. No. 3,372,196; Kollonitsch; U.S. Pat. No. 3,445,519, Engelhardt, U.S. Pat. No. 3,922,305; and Kyburz et. al., U.S. Pat. No. 4,136,116. Related foreign patents include French Pat. No. 632,244, Swiss Pat. No. 415,611; Canadian Pat. No. 742,262, Tishler et. al.; and Australian Pat. No. 281766, Tishler et. al.
The use of protriptyline as a antidepressant has been discussed in several medical journal articles including Dorfman, W.; The Use Of Protriptyline (MK-240) As A Antidepressant A Preliminary Report, Am.J.Psych, 126, 594-595; (1963); Vaisberg, M., Protriptyne in the Treatment of Depressive States, Dis. Nerv. Syst. 25, 110-111 (1964); Oltman, J. and Friedman, S. Protriptyline in the Treatment of Depressive Reactions, Am.J. Psych. 122, 582-584 (1965); Krakowski, A. J., Protriptyline in Treatment Of Severe Depressions; A Long Range Pilot Study, Am.J. Psych. 121, 807-809, (1965); Weinstock, R. et. al., Effects of Protriptyline and Perphenazine in Neurotic Depressed Outpatients, J. Clin. Phar., 627-630, (1975), Whyte, S. F. et. al. Plasma Concentrations of Protriptyline and Clinical Effects in Depressed Women, Brit. J. Psych 128, 384-390, (1976) and Gilbert, M. and Koepke, H., Oxazepam-Protriptyline: A Double-Blind Phase II Evaluation of the Efficacy and Safety of the Combination Versus Placebo in Neurotic, Depressed and Anxious Psychiatric Outpatients, Current Therapeutic Research 18, No. 6, 825-838 (1975).
In addition to their use for the treatment of depression, tricylic compounds have been considered to be useful in the treatment of alcoholism, eating disorders, anxiety syndromes and some cases of obsessive compulsive disorders. For example, one of the current uses being investigated is the treatment of adult women with depression problems associated with premenstrual syndrome.
The tricylic compounds in general and protriptyline in particular have been used and are well accepted for the treatment of adult depression. However, the treatment of adults for depression has no relationship to the treatment of children for ADS or ADD since ADS or ADD are not considered to be affective disorders and diagnostic standards exclude childhood depressive disorders. (See previous discussion).
Adult depression is an entirely separate diagnostic category and does not include any of the diagnostic standards for attention deficit syndrome or disorder. Protriptyline is considered to be useful only in the treatment of adults with retarded depression characterized by hypersomulance, withdrawal from interpersonal activities and relationships, decreased energy levels, inertia, and lack of interest in most areas of life.
Adult depression is now considered to actively involve the serotonine pathway, and protriptyline is specific for the noradrenergic pathway. Thus, no common neurobiochemical pathway is known. Kashana, J. H. and Cantwell, D. P., Etiology and Treatment of Childhood Depression: A Biopsychological Perspective. Child Psych & Human Dev. 23(3), 348-351, (May, 1984).
These tricyclic compounds have not been used in the treatment of childhood mental health problems generally and ADS in particular. Occasionally imipramine, desipramine and amitriptyline have been used to treat childhood depression and enuresis with imipramine commonly being the drug of choice. No mention has been made of the use of protriptyline. Further, it is widely acknowledged that childhood depression as an illness varies significantly from ADS or ADD since ADS or ADD are not considered affective disorders.
Not only has the use of protriptyline been restricted, but the product information distributed by the manufacturer of the drug states that this drug is not recommended for the treatment of children. Although in the Vaisberg Article previously discussed, one 10 year old boy was treated with protriptyline, halting his enuresis, there have been no suggestion that the use of protriptyline would be effective for the treatment of ADS or ADD. In fact, protriptyline has not even been considered for the treatment of childhood depression.
Accordingly, it is an object of the present invention to use protriptyline for the treatment of childhood mental health problems.
It is a further object of this invention to use protriptyline in the treatment of Attention Deficit Syndrome (or Disorder) in children.
These and other objects, as well as the scope, nature, and utilization of the invention will be apparent to those skilled in the art from the following description and appended claims.